Path Opens to Wide-Ranging New Antidotes

AP

Published: August 26, 1990

STATE COLLEGE, Pa., Aug. 25—
Scientists who successfully bonded metal ions to an antibody say the procedure could be the first step toward one day creating antidotes that could neutralize chemical weapons, drug overdoses and most poisons.

The metal ions act as catalysts that can convert poisons to harmless substances inside the human body, said Stephen J. Benkovic, a chemistry professor at Pennsylvania State University.

''It could be used as a detoxifying agent for people who have taken a drug overdose and can be used against environmental pollutants,'' Dr. Benkovic said in an interview. When the military learned of the early laboratory success, officers asked for a briefing about possible applications in chemical warfare, he said.

The new substances, or metalloantibodies, can be made by altering the amino acid sequence of the antibody to make it easier to bind with a metal, said Sheila A. Iverson, who is working on the project at the Research Institute of Scripps Clinic in La Jolla, Calif.

Broadening Antibodies' Range

Antibodies are proteins produced naturally in the bloodstream and are integral components of the human immune system that attack invading bacteria and viruses. Attaching metal ions to them could broaden their range to combat strong toxins the body cannot fight.

Through different modifications, antidotes could one day be developed for any poison, making metalloantibodies a logical defense against chemical warfare, said David Lenz, an Army pharmacologist at the Aberdeen Proving Ground in Maryland.

''It can be used not so much to demoralize the enemy, but to reduce the threat of him using chemical weapons at all,'' Mr. Lenz said. ''They won't use them if they're not going to work.'' Development of antibodies for humans is years away, but recent laboratory successes are promising, he said.

Could Treat Drug Overdoses

''By having a metal ion embedded in the protein, it can now catalyze many diverse chemical reactions,'' said Dr. Benkovic, whose work with Richard Lerner of the Scripps Clinic was published in the journal Science on Aug. 10.

A metalloantibody could be developed to treat cocaine overdoses, Dr. Benkovic said. ''The antibody can convert poisons by acting as a catalyst,'' he said.

''It changes the first toxin it sees, then keeps on going until there's no toxin left. The antibody can be engineered to bind toxins or chemically change them.'' With zinc or copper attached, the new antibody could be injected into a person even before exposure. Chemical poisons rendered harmless would be excreted.

In research conducted from April to June, Dr. Benkovic and Mr. Lerner experimented on genetic material exposed to fluorescein, which emits a known amount of energy.

After altering the genetic material's antibodies with a copper ion, they exposed the new product to fluorescein. ''When metal binds to fluorescein, it should change the energy level,'' Ms. Iverson said. The altered antibody did change the energy readings, so researchers knew the metal ion had been successfully added to the antibody.

To make the process work on animals or humans, scientists must explore the structures of other antibodies and determine what chemical alterations would be needed to attach a metal ion to them.

If successful, metalloantibodies could one day be mass-produced, Dr. Benkovic said. ''We have shown that you can bind a metal ion to an antibody. he said. It's a start.''